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Objective To investigate the role and mechanism of NLRP3/Caspase-1/IL-1 β inflammasome pathway in the formation of aortic dissection in mice.Methods Fifty male C57BL/6 mice(3 weeks old,body weight 10~13 g)were divided into control group(n =10,normal diet),β-aminopropionitrile(BAPN)group[n =20,drink water containing 1 g/(kg·d)BAPN],and BAPN+MCC950 group[n=20,drink water containing 1 g/(kg·d)BAPN and intraperitoneal injection of 20 mg/(kg·d)NLRP3 inhibitor,MCC950]by random sampling.Water intake,body weight,incidence of aortic dissection and aortic dissection-related mortality were recorded.The inflammatory infiltration in the aorta was observed with HE staining,elastic fiber breakage was observed by elastic Van Gieson(EVG)staining,average fluorescence intensity of NLRP3,IL-1β,α-SMA and OPN was detected by immunofluorescence assay,and protein expression levels of NLRP3,Caspase-1,ASC,IL-1β,α-SMA and OPN were measured with Western blotting.Results No aortic dissection or death was observed in the control group.The BAPN group had an incidence of aortic dissection of 80%,aortic dissection-related mortality of 35%,and obvious broken elastic fibers and inflammatory infiltrate in the aortic wall,and increased expression levels of NLRP3,Caspase-1,ASC and IL-1 β,decreased contractile α-SMA and increased synthetic protein OPN when compared with the control group(P<0.05).While MCC950 treatment decreased the incidence of aortic dissection(80%vs 35%,P=0.004)and aortic dissection-related mortality(35%vs 15%,P=0.144),alleviated the broken elastic fibers and inflammatory infiltrate in the aortic wall,and down-regulated the expression of NLRP3,Caspase-1,ASC and IL-1β,enhanced contractile α-SMA and decreased the synthetic protein when compared with the BAPN group(P<0.05).Conclusion The occurrence of aortic dissection in mice is associated with activation of NLRP3/Caspase-1/IL-1 β inflammasome pathway.NLRP3 inhibitor,MCC950,can reduce the occurrence of aortic dissection and show a protective effect on blood vessels.
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Objective:To explore the effect of formative evaluation based on Rain Classroom on clinical skills teaching.Method:s A total of 70 students in clinical medicine from Grade 2016 were enrolled and divided into experimental group ( n=35) and control group ( n=35). The experimental group adopted Rain Classroom combined with formative evaluation, while the control group used conventional teaching method and evaluation. Test scores of the two groups were compared and students' satisfaction was collected via questionnaire. T-test was performed using SPSS 17.0. Result:The total score of clinical skills test in the experimental group was (84.11±7.76), which was significantly higher than that in the control group (74.37±12.58), and the difference was statistically significant ( P<0.05). According to the questionnaire survey, the experimental group was significantly better than the control group in terms of enhancing learning interest, improving knowledge comprehension, clinical skills, clinical thinking and analytical ability, as well as better satisfaction towards teaching ( P<0.05). Conclusion:Formative evaluation based on Rain Classroom is helpful to improve the teaching effect on clinical skills and comprehensive abilities of students, so as to promote their overall development.
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Objective To detect the expression of tumor necrosis factor-α-induced protein-8 like-3 (TIPE3) in colonic mucosa of patients with colon cancer,and to analyze the correlation between its abnormal expression and clinicopathological features of patients with colon cancer.Methods The expression of TIPE3 mRNA in 58 cases of colon cancer and tumor adjacent tissues was detected by realtime polymerase chain reaction (RT-PCR).The expression of TIPE3 at protein level in 83 cases of colon cancer and tumor-adjacent tissues was determined by SP immunohistochemistry.Nonparametric rank-sum test and chi-square test were performed for statistical analysis.Results The relative expression of TIPE3 mRNA in the colon cancer tissues was 0.719 (0.104 to 0.887),which was lower than that of tumor-adjacent tissues (4.770,1.732 to 6.800),and the difference was statistically significant (Z=-6.345,P<0.05).There was no statistically significant difference in the expression of TIPE3 mRNA in colon cancer tissues between different gender,age and TNM stage (all P>0.05).The expression of TIPE3 mRNA in group of patients with lymph node metastasis (0.113,0.061 to 0.375) was lower than group of patients without lymph node metastasis (0.489,0.327 to 0.956;Z=3.815,P<0.01).The expression of TIPE3 mRNA of patients survived less than five years after operation (0.104,0.049 to 0.220) was lower than that of patients survived over five years (0.482,0.266 to 0.908;Z=-3.653,P<0.01).The expression of TIPE3 mRNA of patients with recurrence after operation (0.188,0.091 to 0.493) was lower than that of patients without recurrence (0.409,0.233 to 1.010;Z=-2.431,P=0.015).The recurrence rate of TIPE3 mRNA high expression group in five years after operation was lower than that of TIPE3 mRNA low expression group (23.1%,6/26 vs 56.2%,18/32);and the difference was statistically significant (x2 =6.508,P<0.05).The expression of TIPE3 at protein level of colon cancer tissues (44.6 %,37/83) was lower than that of tumor-adjacent tissues (68.7 %,57/83;x2 =8.004,P<0.05).The expression of TIPE3 at protein level was not correlated with age and gender (both P>0.05).The positive expression rate of patients at stage Ⅱ was higher than that of patients at stage Ⅲ (60.5%,23/38 vs 29.7%,1/37);and the difference was statistically significant (x2 =7.174,P< 0.05).The positive expression rate of TIPE3 in group of patients with lymph node metastasis was lower than that of groups of patients without lymph node metastasis (28.2%,11/39 vs 59.1%,26/44),and the difference was statistically significant (x2=7.983,P =0.005).Conclusions The expression of TIPE3 in colon cancer tissues is lower than that in tumor-adjacent tissues.Furthermore,it is correlated with lymph node metastasis,recurrence rate and survival rate.TIPE3 may be involved in the genesis,development,invasion and metastasis of colon cancer.
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Intestinal microecology is an important and complex biological system necessary for human health.Its disorder is involved in the development of various diseases of human body.The technology of intestinal microbiota transplantation can effectively regulate the intestinal flora,repair the imbalance of the intestinal microecology,and bring a new breakthrough for the treatment of many diseases of gastrointestinal tract and outside gastrointestinal tract.However,there is still no systematic and complete management standard for intestinal microbiota transplantation technology.This paper discussed related content involved in standardized management of intestinal microbiota transplantation technology and reflected the ethical problems involved in standardized management from the perspective of medical ethics,in order to promote the clinical application of intestinal microbiota transplantation technology.
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BACKGROUND: In alveolar cleft patients, the amount of bone stock after alveolar bone grafting is mostly measured and analyzed by two-dimensional imaging, which can result in a large error. OBJECTIVE: To evaluate the 6-month osteogenesis of alveolar bone graft in alveolar cleft patients using cone beam CT. METHODS:Alveolar bone grafting was performed in 25 patients with unilateral complete alveolar cleft. The patients were folowed up for 6 months after surgery and the osteogenesis of the bone graft was evaluated by CBCT. RESULTS AND CONCLUSION:After the surgery, the labial bone support was better than the palatal one. There were significant differences in the alveolar bone thickness of the cleft region and the normal region of the central incisor as wel as the alveolar bone thickness of the cleft region and the normal region of the canine tooth 0 mm distant to the alveolar crest. These findings indicate that the palatal bone support is less than the labial one, and the bone support of the central incisor is not satisfactory, which provide the basis for the tooth movement in the alveolar bone grafting and the orthodontics treatment.
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Objectives To investigate the mutational characteristics of MSX1 and PAX9 genes in a family affected by non-syndromic oligodonti so as to study the pathogenesis of oligodontia from a molecular prospective. Methods A family with oligodontia, but of different descent and unrelated healthy controls were enrolled in our study. Genomic DNA was isolated from the blood samples. Mutation analyses were performed by amplifying MSX1 and PAX9 exons and sequencing the products. Results DNA sequencing revealed a novel missense mutation c.348C>T in a highly conserved homeobox sequence of MSX1 and a known polymorphisms c. 469+35- c.469+45del in exon 1 and in intron in the two patients and in two unrelated healthy controls. But we did not detect any mutation in PAX9. Conclusion Our finding suggests the samesense mutation (c.348C>T) and the polymorphisms (c.469+35- c.469+45del) may be responsible for oligodontia phenotype in this Chinese family.
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Objective:To evaluate the effects of periodontal treatment with scaling and root planning supplemented with chlorhexidine on plasma lipids in patients with chronic periodontitis and hyperlipidemia(CPH).Methods:6 1 patients with CPH were randomly as-signed into control-treatment group(n=30)and intensive-treatment group(n=31).Patients in the control-treatment group underwent a standard cycle of supragingival mechanical scaling and polishing.Patients in the intensive-treatment group underwent the adjunctive full-mouth intensive removal of subgingival dental plaque biofilms with the use of scaling and root planning.Periodontal parameters,to-tal cholesterol(TC),triglycerides(TRG),high-density lipoprotein(HDL)and low-density lipoprotein(LDL)were measured before treatment and 2 and 6 months after treatment.Results:2 and 6 months after treatment,TRG was significantly lower in the intensive-treatment group than that in the control-treatment group(P<0.05),the levels of HDL were significantly higher(P<0.05);however, the levels of total cholesterol and LDL,in the intensive-treatment group were not significantly different from those in the control-treat-ment group 2 and 6 months after therapy.Conclusion:Intensive periodontal treatment may improve serum lipid levels in patients with hyperlipidemia and chronic periodontitis.
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Objective To determine the function of conserved amino acids in the fusion-promoting domain of Newcastle disease virus (NDV) hemagglutinin-neuraminidase (HN) protein,clearly understanding mechanism of cell fusion.MethodsUsing a PCR-based site-directed mutagenesis method and the method of homology recombination occurred in vivo to change six conservative amino acids into alanine respectively.Wild type (WT) and all mutant HN proteins were exepressed in BHK-21 cells by the vacciniaT7 RNA polymerase expression system.The amount of each HN protein at the cell surface was determined by fluorescence-activated cell sorter (FACS).Cell fusion efficiency,hemadsorption activity (or receptor binding activity) and neuraminidase activity were determined.Results There was no statistic difference of cell surface expression among WT and each mutant HN protein ( P<0.05 ).Cell fusion efficiency of each mutant protein decreased to some extent,especially 1103A decreased to 14.2% in head.Hemadsorption activity of mutant proteins were reduced in different extent,the maximum reduction of which was also 1103A,28.2% of wt NDV HN.There was different neuraminidase activity among each mutant HN protein.L74A increased slightly to 118.6%.L110A decreased most to 5.2%.I103A decreased second most to 5.7%.Conclusion Conserved amino acids in fusion-promoting domain of NDV HN played an important role in cell fusion.I103 was identified as a key amino acid in this domain.
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Objective To study the variation and characteristics of HIV-1 tat exon 1 gene from a patient with AIDS dementia complex( ADC), so as to research the pathogenesis of ADC. Methods The tat gene was amplified with nested PCR from genomic DNA which was extracted from lymph node, spleen and different brain tissues( meninges, grey matter from frontal cortex, white matter from frontal cortex, temporal cortex and basal ganglia) of a patient who died of ADC. PCR products were cloned into the pGEM-T vector,after transformation and selection by ampicillin and blue/white spotting. Five of positive clones were sequenced. HIV-1 tat sequences were processed with BioEdit and MEGA4. With the softwares, Neighbor-Joining tree, p-Distances, values of ds/dn, and analysis of amino acid motifs were all done. Results The samples were all identified as HIV-1 B and genetic variation exists in HIV-1 tat isolated from different tissue;Compared with HXB2, sixteen sites of the amino acid seque nce coded by the HIV-1 tat gene which was isolated from the patient changed. In addition, part of the changes were different between periphery and brain,especially, the five Q54R changes from basal ganglia and one Q54R change from temporal cortex are deserve to follow with interest. Conclusion Variations exist in the HIV-1 tat genes extracted from the ADC patient and the variations from peripheral and central nerve tissues were different, whether the variations concerned with the pathogenesis of ADC need more research.
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Objective To investigate the effects of hyperbaric oxygen preconditioning (HBOP) on brain edema, inflammatory reaction and neuronal cell apoptosis induced by experimental hemorrhage in rats. Method Eighteen male Spraque-Dawley rats, weighing 300 - 350 g,received five successive sessions of HBOP with 3 atmosphere absolute pressure and 100% O2 one hour daily for five successive days, and other eighteen rats received five successive sessions of pretreatment with one atmosphere absolute pressure, air, one hour daily for five successive days. Twenty-four hours after the final pre-conditioning, rats received an infusion of 100 μL autologous blood into the basal ganglion. Seventy-two hours later, rats were sacrificed for brain edema measurements in 12 rats of each group. The histopathological changes around the hematoma were observed microscopically, and the neuronal cell apoptosis was detected by using the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) in six rats of each group. Data of brain water content were analyzed by using Stata 7.0 software and statistical analysis was carried out by two-tailed Student t -test. Results Compared with the control group, HBOP significantly attenuated brain edema 72 hours after intra-cerebral hemorrhage in experimental rats (81. 6± 0. 7% vs. 82. 8± 0.9%, P < 0.01). Inflammatory cell infiltration and neuronal cell apoptosis were also significantly decreased in the HBOP group. Conclusions HBOP protects the rats against brain edema formation, and quells inflammatory reaction and neuronal cell apoptosis following intra-cerebral hemorrhage in experimental rats.
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Objective To evaluate the prognostic impact of a wide spectrum of pathologic parameters in a consecutive series of homogenously treated and well-characterized patients with stage Ⅰ and Ⅱ colorectal cancer, and to investigate the prognostic value of lymph node occult disease (micrometastasis) in disease-free survival rate detected by immunohistochemistry with epithelial membrane antigen and carcinoembryonic antigen. Methods The study included 126 patients operated on by a single surgeon for stage Ⅰ and Ⅱ colorectal tumors. The postoperative follow-up was performed for 64 to 106 months. At least 10 lymph nodes were harvested and examined in all the specimens. The prognostic value of 10 pathologic parameters, including lymph node occult disease (micrometastasis) detected by immunohistochemistry was investigated. Results Multivariate analysis identified lymphatic vessel invasion (absent or present;P=0.009) in lymph node positive and negative by immunohistochemistry. The five-year disease-free survival rates were 78.7%, 65.5% and 43.8% for the lymph node negative, isolated tumor cells and micrometastasis groups, respectively. There was significant difference between the lymph node negative and micrometastasis groups (P=0.005). However, the difference between the lymph node negative and isolated tumor cells groups was not statistically significant (P=0.144). Conclusions We propose that for patients found micrometastasis in lymph node with high-risk stage Ⅰ and Ⅱ colorectal cancer, adjuvant therapies are justified and effective.
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Objective To investigate mutation patterns in core promoter(CP)region of hepatitis B virus(HBV).Methods HBV DNA was extracted from sera of patients with chronic HBV infection.The CP sequence was amplified by polymerase chain reaction(PCR)and cloned into pMD19 T vector.The positive clones were then sequenced.The sequences were compared with known HBV genome in GenBank to identify the mutation sites and patterns of patients with chronic HBV infection.Results There were 74 clones from 21 patients with chronic HBV infection which were sequenced.The sequence comparisons showed that there was a 234-nucleotide deletion in CP region of HBV genome in 54 clones and a 245-nucleotide deletion in one clone.These deletion regions included CP,HBeAg initiation codon and direct repeat sequence(DR)Ⅰ regions,which named CP deletion(CPD).A1585T replacement mutation was also found in HBV strain with CPD,which indicated that there was linkage between these two mutations.Conclusions A novel mechanism of HBeAg negative chronic hepatitis B is observed,which includes deletions of CP and HBeAg initiation codon.Meanwhile,a simple and useful PCR method is developed to detect CPD.
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ted in a loss of cell fusion,which suggests the 928 site on G2 is crucial for cell fusion and the fusion peptide is likely on G2.
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Objective To evaluate the impact of pathologic parameters and lymphatic mierometastasis on 5-year disease-frtee survival in patients with stages Ⅰ and Ⅱ colorectal cancer.Methods Surgical operation was performed in 126 patients with stage Ⅰ and Ⅱ colorectal cancer.Sixteen (range,10-28)lymph nodes were harvested in each specimen and immunohistochemical staning was performed. Theimpact of pathologic parameters and lymphatic micrometastases in survival was estimated by KaplanMeier.Results The mean follow up time was 64.11 (range,64-106) months. Multivariate analysisrevealed that lymphatic vessel invasion and depth of tumor invasion were correlated with positive CEA in lymph node,and unrelated with clinical pathologic factors.There was no significant difference between pathologic parameters and five year disease-free survival rates. The five-year diseasse-free survival rates was 75.4 percent in CEA negative patients,68.2 percent in patients with isolated tumor cells,and 46.2 percent in patients positive for micrometastasis.There was no significant difference in 5 year disease-free survival between CEA negative patients and patients with isolated tumor cells (P=0.245).However,the5-year disease-free survival was lower in patients positive for micrometastases compared to CEA negativepatients (P=0.003).Conclusions The presence of micrometastases in patients with stages Ⅰ and Ⅱ colorectal cancer may result in poor prognosis and high recurrence,and adjuvant chemotherapy will bejustified and effective.
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<p><b>BACKGROUND</b>To investigate the relationship between immune status and rubella virus (RV) infection of central nervous system (CNS).</p><p><b>METHODS</b>BALB/c mice were given dexamethaxone and cytoxan before RV JR23 strain infection. Immune functions and RV invasion to CNS were assayed at 21 days postinfection via abdominal cavity and their relationship was analyzed.</p><p><b>RESULTS</b>T cell functions of cytoxan group were obviously worse than those of other groups (P <0.05) by MTT method. Infection rates of dexamethaxone and cytoxan and the group without any intervention were 60%, 90% and 50% (P >0.05), respectively. Cellular immune functions of the mice with CNS infection were obviously worse than those of the mice without CNS infection (P <0.001). Specific antibodies (Ab) were assayed in all groups with ELISA and the results showed that there were no significant differences among groups (P >0.05), neither between the groups with and without CNS infections.</p><p><b>CONCLUSIONS</b>RV infection of CNS may relate to cellular immune status before specific antibody was produced in the body.</p>
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Animals , Female , Male , Mice , Antibody Specificity , Central Nervous System Infections , Allergy and Immunology , Virology , Immunity, Cellular , Mice, Inbred BALB C , Rubella , Allergy and Immunology , Rubella virus , Allergy and Immunology , T-Lymphocytes , Allergy and ImmunologyABSTRACT
OBJECTIVE To investigate the manifestation,fungal spectrum,diagnosis,antifungal therapy and(outcome) of deep fungal infection(DFI) in patients with hematopoietic malignancies.METHODS Fifty-two(patients) of SFI admitted in Shandong Provincial Hospital during Oct 1998 to Sept 2004 were enrolled in this(investigation,) including 34 males and 18 females with mean age of 54 years old.Clinical data,such as manifestation,fungal(spectrum,) treatment and outcome,were observed prospectively and retrospectively.RESULTS Lower respiratory tract,gastrointestinal tract,urinary tract and blood were the main DFI infection sites by order of prevalence.The clinical manifestation was various among cases.Pathogen detection determined the subtypes of fungi were Candida albicans(57.14%),C.tropicalis(21.43%),yeast(47.14%),C.parapsilosis(7.14%),and Aspergillus((5.36%).) Nystatin,fluconazole,flucytosine,and(amphotericin) B were used alone or in(combination) to treat DFI.The rates of curing,improvement and death were 44.23%,23.08% and 32.69%,(respectively).(Among) 52 cases,25(48.08%) were occurred during Oct 2002 to Sept 2004,compared with 27((51.92%)) during Oct 1998 to Sept 2002,suggested the elevated incidence of DFI.CONCLUSIONS The incidence of DFI in patients with hematopoietic malignancies is increasing these years.The clinical manifestation of DFI may be nonspecific.It is critical to pay more attention to the fungal infection among the high-risk patients,therefore fungus detection from various(samples) should be recommended for the sake of early diagnosis of DFI. Though(C.albicans) remains the top in pathogen spectrum analysis,infection of other fungi tends to increase.The mortality of DFI is still very high thus more investigations about early diagnosis and treatment of DFI should be conducted.